title: Pharmacological characteristics of endothelin receptors on sheep rectal blood vessels.
abstract: Haemorrhoids is associated with high blood flow of the anorectal region. The question of whether pharmacological manipulation of vascular supply can relieve the symptoms of haemorrhoids has been raised. In order to undertake this type of clinical investigation, it is first essential to gain a better understanding of the properties of vascular receptors that may regulate blood flow into anal cushions and haemorrhoids. Due to the limited availability of human anorectal specimens and the good reliability of sheep tissue as an experimental model of human anorectal diseases, we studied the properties of endothelin receptors in sheep rectal artery (SRA) and vein (SRV), the vessels contributing to the blood flow of haemorrhoidal plexus, using isometric tension recordings. We found that endothelin-1 and sarafotoxin 6a were very potent constrictor agents in both SRA and SRV. The selective ET(A) receptor antagonist PD156707 (100 nM) produced a parallel rightward displacement of ET-1-induced contractions in both vessels and abolished sarafotoxin 6a-induced contractions in the SRA. PD156707 (3 μM) practically abolished contractions to ET-1 in the SRA, suggesting that the response is entirely mediated by ET(A) receptors. While, the selective ET(B) receptor antagonist BQ788 (100 nM) caused no significant change in ET-1-induced contractions in both vessels, a minor role for ET(B) receptor subtype to responses to sarafotoxin 6a in the artery was suggested.
authors.affiliation: Division of Gastrointestinal Surgery, Queen's Medical Centre, University of Nottingham, UK. bolloon@hotmail.com
authors.forename: Varut
authors.initials: V
authors.lastname: Lohsiriwat
authors.forename: John H
authors.initials: JH
authors.lastname: Scholefield
authors.forename: Michael R
authors.initials: MR
authors.lastname: Dashwood
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Wilson
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001808:Blood Vessels / Q000187:drug effects*; D004149:Dioxoles / Q000494:pharmacology / Q000627:therapeutic use; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D006484:Hemorrhoids / Q000188:drug therapy; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011189:Potassium Chloride / Q000378:metabolism; D017466:Receptors, Endothelin / Q000187:drug effects* / Q000502:physiology; D012007:Rectum / Q000098:blood supply; D012756:Sheep; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014757:Viper Venoms / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D004149:Dioxoles; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; C093321:PD 156707; D010880:Piperidines; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C086539:BQ 788; D011189:Potassium Chloride